Objective: Management of heavily pre-treated platinum-resistant ovarian cancer remains a therapeutic challenge. Outcomes are poor with non-platinum, single-agent chemotherapy (CT); however, molecularly targeted anticancer therapies provide new options. Methods: This open-label, investigator-initiated, phase 2 umbrella trial (NCT03699449) enrolled patients with platinum-resistant ovarian cancer (at least 2 prior lines of CT and Eastern Cooperative Oncology Group 0/1) to receive combination therapy based on homologous recombination deficiency (HRD) and programmed death ligand 1 (PD-L1) status determined by archival tumour sample assessment. HRD-positive patients were randomised to either olaparib 200mg bid tablet + cediranib 30mg qd (arm 1) or olaparib 300mg bid tablet + durvalumab 1,500mg q4w (arm 2). HRD-negative patients were allocated to either durvalumab 1,500 mg q4w + pegylated liposomal doxorubicin (PLD) or topotecan or weekly paclitaxel (6 cycles; arm 3, those with PD-L1 expression) or durvalumab 1,500 mg q4w + tremelimumab 75mg q4w (4 doses) + PLD or topotecan or weekly paclitaxel (4 cycles; arm 4, those without PD-L1 expression). Arm 5 (durvalumab 1,500 mg q4w + tremelimumab 300mg [1 dose] + weekly paclitaxel [60 mg/m2 D1,8,15 q4w for 4 cycles] was initiated after arm 4 completed. The primary endpoint was objective response rate (ORR; Response Evaluation Criteria in Solid Tumours 1.1). Results: Between Dec 2018 and Oct 2020, 70 patients (median 57 years; median 3 prior treatment lines [range 2–10]) were treated (n=16, 14, 5, 18, and 17, respectively). Overall ORR was 37.1% (26/70, 95% confidence interval=25.9, 49.5); 2 achieved complete response. ORR was 50%, 42.9%, 20%, 33.3%, and 29.4%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients, respectively. No TRAEs leading to treatment discontinuation and no grade 5 TRAEs were observed. Conclusion This study, the first biomarker-driven umbrella trial in platinum-resistant recurrent ovarian cancer, suggests clinical utility with biomarker-driven targeted therapy. All treatment combinations were manageable, and without unexpected toxicities.

Purpose: To profile various clinical characteristics of sleep bruxism (SB) patients with idiopathic facial pain (IFP) in the orofacial region. Materials and Methods: We analyzed 28 SB patients among 210 patients with IFP complaints. The profiles were evaluated using patient charts including gender, age, pain duration, pain location, pain intensity and affected areas by pain. Results: SB with IFP occurred more often in females (85.7%) than males (14.3%). The mean age at presentation was 48.9 years. The most common IFP sites of SB patients were the right maxilla (28.6%) and the right mandible (25.0%). The pain complaints occurred mostly in 2 teeth or areas (50.0%), followed by 1 area (28.6%) and then in ≥ 3 teeth or areas (21.4%). The mean pain intensity was 5.9 on a visual analogue scale from 0 to 10. The pain was spontaneous in 20 patients (71.4%), and the mean pain duration was 24.4 months. Conclusion Identification of clinical characteristics of SB patients with IFP could be useful in the diagnosis of various IFP patients and beneficial in decreasing unnecessary care to reduce IFP. Further studies with larger number of subjects and extended duration are required for more systemized diagnostic methods and development of future treatment guidelines.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Objectives: . Human amniotic membrane extract (AME) is known to contain numerous bioactive factors and anti-inflammatory substances. However, the anti-inflammatory effects of AME on the middle ear (ME) mucosa are unclear. This study assessed the effects of AME on the growth of the ME mucosa in response to bacterially-induced otitis media (OM). Methods: . OM was induced by inoculating nontypeable Haemophilus influenzae (NTHi) into the ME cavity of rats. ME mucosal explants were cultured in AME concentrations of 0, 5, 10, or 50 μg/mL. The area of explant outgrowth was measured in culture and analyzed at 1, 3, 5, and 7 days after explantation. The expression of Ki-67, mucin 5AC (MUC5AC), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) in the explants was also evaluated using quantitative polymerase chain reaction (PCR) and immunocytochemistry (ICC). Results: . The NTHi-induced ME mucosa growth increased gradually over the 7-day culture period in all explants at different AME concentrations. There was a trend for mucosal growth inhibition at higher concentrations of AME, although the growth was not significantly different among the groups until day 5. The ME mucosal explants treated with the 50 μg/mL concentration of AME showed significantly suppressed growth on postexplantation day 7 compared with other explants on the same day. PCR and ICC staining revealed that the expression of Ki-67, MUC5AC, TNF-α, and IL-10 further decreased in the explants with higher concentrations of AME than in those with lower concentrations of AME. Conclusion . Our results showed that higher concentrations of AME reduced the mucosal proliferative response in bacterial OM in rats. These findings provide evidence that AME has an influence on the inflammatory and proliferative responses to NTHi infection in ME mucosa.

PURPOSE: Implant surface modification and implant design are the principle targets for achieving successful primary stability. The aim of this study was to measure implant stability quotient (ISQ) values of sandblasted, large-grit, acid-etched (SLA) implants with tapered straight body design during the healing period, and to determine the various factors affecting implant stability. MATERIALS AND METHODS: To measure implant stability, resonance frequency analysis (RFA) was performed in 26 patients (13 women and 13 men) with 44 SLA implants with tapered straight body design. Implant stability (ISQ values) was evaluated at baseline and healing abutment connection (12 weeks), and the correlations between RFA and insertion torque (IT), bone quality, and jawbone were determined. RESULTS: The mean ISQ value of the implants was 69.4 ± 10.2 at the time of implant placement (baseline) and 81.4 ± 6.9 at the time of healing abutment connection (P < 0.05). Significant differences were found between RFA and bone quality and between RFA and jawbone (P < 0.05). No significant differences were found between RFA and IT, insertion area, fixture diameter, and implant length (P > 0.05). CONCLUSION: ISQ values of SLA implants with tapered straight body design were high at baseline and healing abutment connection. It was concluded that SLA implants with tapered straight body design show improved primary and secondary stability, and that immediate or early loading may be applicable.
Female ; Humans ; Torque

BACKGROUND: Vitamin D plays an important role in the immune response against infection. The purpose of the present study was to investigate the influence of vitamin D deficiency on the progression of otitis media (OM) using an experimental rat model. METHODS: Four-week-old male Sprague-Dawley rats (n=72) were divided into two groups based on their diet: a control diet group (n=36) and a vitamin D-deficient diet group (n=36). After 8 weeks of diet, experimental OM was induced by inoculation of non-typeable Haemophilus influenzae in the middle ear cavity. The rats were evaluated with otomicroscopy to determine the inflammation in the middle ear mucosa on days 1, 2, 4, 7, and 14 post-inoculation. Bullae from sacrificed rats were collected and analyzed histologically. RESULTS: The middle ear mucosa from rats with vitamin D deficiency showed a significantly higher thickness than that of controls during the course of OM. The maximum mucosal thickness was 56.0±9.1 µm in the vitamin D deficiency group, and 43.9±9.8 µm in the control group, although there was no significant difference in the tympanic membrane score between the two groups evaluated with otomicroscopy. An immunohistochemical study showed increased expression of interleukin 6 (IL-6) and tumor necrosis factor α in rats manifesting vitamin D deficiency and decreased expression of IL-10 compared with controls. CONCLUSION: Our results showed that vitamin D deficiency may exacerbate the pathophysiological changes of OM via altered cytokine production. Therefore, maintaining vitamin D status in the optimal range may be beneficial for proper management of OM.
Animals ; Diet ; Ear, Middle ; Haemophilus influenzae ; Humans ; Inflammation ; Interleukin-10 ; Interleukin-6 ; Male ; Models, Animal ; Mucous Membrane ; Otitis Media* ; Otitis* ; Rats* ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; Tympanic Membrane ; Vitamin D Deficiency* ; Vitamin D* ; Vitamins*

BACKGROUND/OBJECTIVES: We investigated the effects of a combination of grape pomace (Vitis labrusca, Campbell Early) and Omija fruit (Schizandra chinensis, Baillon) ethanol extracts on lipid metabolism and antioxidant defense system in diet-induced obese mice. MATERIALS/METHODS: Forty male C57BL/6J mice were divided into four groups and fed high-fat diet (control group, CON) or high-fat diet added 0.5% grape pomace extract (GPE), 0.05% Omija fruit extract (OFE) or 0.5% GPE plus 0.05% OFE (GPE+OFE) for 12 weeks. RESULTS: In contrast to the GPE- or OFE-supplemented groups, the GPE+OFE group showed significantly lower body weight and white adipose tissue weights than the CON group. Moreover, GPE+OFE supplementation significantly decreased plasma total cholesterol and increased the plasma HDL-cholesterol/total-cholesterol ratio (HTR) compared to the control diet. The hepatic triglyceride level was significantly lower in the GPE+OFE and GPE groups by increasing beta-oxidation and decreasing lipogenic enzyme compared to the CON group. Furthermore, GPE+OFE supplementation significantly increased antioxidant enzyme activities with a simultaneous decrease in liver H2O2 content compared to the control diet. CONCLUSIONS: Together our results suggest that supplementation with the GPE+OFE mixture may be more effective in improving adiposity, lipid metabolism and oxidative stress in high-fat diet-fed mice than those with GPE and OFE alone.
Adipose Tissue, White ; Adiposity ; Animals ; Body Weight ; Cholesterol ; Diet ; Diet, High-Fat ; Ethanol* ; Fruit* ; Humans ; Lipid Metabolism* ; Liver ; Male ; Mice ; Mice, Obese* ; Oxidative Stress ; Plasma ; Triglycerides ; Vitis* ; Weights and Measures

Extrahepatic bile duct can be compressed by right hepatic artery (RHA) and cause a variety of hepatobiliary symptoms. This condition is referred to as RHA syndrome. A 20-year-old man was admitted because of jaundice. No stones or tumor were visible on CT scan and endoscopic retrograde cholangiopancreatography. However, RHA was seen traversing and compressing the mid common bile duct (CBD) with resultant upstream dilatation. The patient was diagnosed with obstructive jaundice due to compression of the CBD by variant RHA originating from gastroduodenal artery. After separation and mobilization of the variant RHA, obstructive jaundice was resolved. Herein, we report a case of a variant form of RHA syndrome that was successfully managed by surgery.
Arteries ; Bile Ducts, Extrahepatic ; Cholangiopancreatography, Endoscopic Retrograde ; Common Bile Duct* ; Dilatation ; Hepatic Artery* ; Humans ; Jaundice ; Jaundice, Obstructive* ; Tomography, X-Ray Computed ; Young Adult

BACKGROUND/AIMS: We used high-resolution impedance manometry (HRIM) to determine the length of breaks on the isobaric contour which would predict incomplete bolus clearance in patients in the sitting position. METHODS: In total, 651 swallows in 71 patients with esophageal symptoms were studied using a solid-state HRIM system in the sitting position. Each swallow was classified as complete or incomplete bolus clearance by impedance criteria and peristaltic integrity was evaluated using 20- and 30-mmHg pressure topography isobaric contours. Correlations between the lengths of the breaks for 20- and 30-mmHg were analyzed. RESULTS: Complete bolus clearance was observed in 83.3% (542/651) of swallows. Breaks of 3 and 7 cm or less were associated with a bolus clearance of 96.8% on the 20-mmHg and 94.7% on the 30-mmHg isobaric contour, respectively (P < 0.001). The areas under the ROC curves for the 20 and 30 mmHg isobaric contours were 0.900 and 0.950, respectively. The sensitivity and specificity for complete bolus clearance were 75.6% and 89.3% for breaks 3 cm or less on the 20-mmHg isobaric contour and 87.9% and 78.7% for breaks 7 cm or less on the 30-mmHg contour (P < 0.001). CONCLUSIONS: Breaks of < 3 cm in the 20-mmHg isobaric contour or < 7 cm in the 30-mmHg isobaric contour were associated with com -plete bolus clearance. The threshold for breaks in the sitting position was greater than previous reports using the supine position and longer breaks predicted incomplete bolus clearance.
Electric Impedance* ; Humans ; Manometry* ; ROC Curve ; Sensitivity and Specificity ; Supine Position ; Swallows